1. Field of the Invention
This invention relates to a relatively simple, yet accurate method and apparatus for monitoring oral anticoagulant therapy that takes into account varying prothrombin times caused by different sensitivities of various thromboplastin formed from rabbit brain, bovine brain, or other sources all used for oral anticoagulant therapy.
2. Description of the Prior Art
To prevent excessive bleeding or deleterious blood clots, a patient may receive oral anticoagulant therapy before, during and after surgery. To assure that the oral anticoagulant therapy is properly administered, strict monitoring is accomplished and is more fully described in various medical technical literature, such as the articles entitled "PTs, PR, ISIs and INRs: A Primer on Prothrombin Time Reporting Parts I and II" respectively published November, 1993 and December, 1993 issues of Clinical Hemostasis Review, and herein incorporated by reference.
These technical articles disclose anticoagulant therapy monitoring that takes into account three parameters which are: International Normalized Ratio (INR), International Sensitivity Index (ISI) and prothrombin time (PT), reported in seconds. The prothrombin time (PT) indicates the level of prothrombin in a plasma sample and is a measure of the coagulation response of a patient. The INR and ISI parameters are needed so as to take into account various differences in instrumentation, methodologies and in thromboplastins' (Tps) sensitivities used in anticoagulant therapy. In general, thromboplastins (Tps) used in North America are derived from rabbit brain, those previously used in Great Britain from human brain, and those used in Europe from either rabbit brain or bovine brain. The INR and ISI parameters take into account all of these various different factors, such as the differences in thromboplastins (Tps), to provide a standardized system for monitoring oral anticoagulant therapy to reduce serious problems related to prior, during and after surgery, such as excessive bleeding or the formation of blood clots.
As reported in Part I (Calibration of Thromboplastin Reagents and Principles of Prothrombin Time Report) of the above technical article of the Clinical Hemostasis Review, the determination of the INR and ISI parameters are quite involved, and as reported in Part II (Limitation of INR Reporting) of the above technical article of the Clinical Hemostasis Review, the error yielded by the INR and ISI parameters is quite high, such as about 13%. The complexity of the interrelationship between the International Normalized Ratio (INR), the International Sensitivity Index (ISI) and the patient's prothrombin time (PT) may be given by the below expression (1),
wherein the quantity ##EQU1## is commonly referred to as prothrombin ratio (PR): ##EQU2##
The possible error involved with the use of International Normalized Ratio (INR) is also discussed in the technical article entitled "Reliability and Clinical Impact of the Normalization of the Prothrombin Times in Oral Anticoagulant Control" of E. A. Loeliger et al, published in Thrombosis and Hemostasis 1985; 53: 148-154, and herein incorporated by reference. As can be seen in expression (1), ISI is an exponent of INR which leads to the possible error involved in the use of INR to be about .+-.13.5% or possibly even more. A procedure related to the calibration of the ISI is described in a technical article entitled "Failure of the International Normalized Ratio to Generate Consistent Results within a Local Medical Community" of V. L. Ng et al, published in Am. J. Clin Pathol 1993; 99: 689-694, and herein incorporated by reference.
The unwanted INR deviations are further discussed in the technical article entitled "Minimum Lyophilized Plasma Requirement for ISI Calibration" of L. Poller et al published in Am J Clin Pathol February 1998, Vol. 109, No. 2, 196-204, and herein incorporated by reference. As discussed in this article, the INR deviations became prominent when the number of abnormal samples being tested therein was reduced to fewer than 20 which leads to keeping the population of the samples to at least 20. The paper of L. Poller et al also discusses the usage of 20 high lyophilized INR plasmas and 7 normal lyophilized plasmas to calibrate the INR. Further, in this article, a deviation of +/- 10% from means was discussed as being an acceptable limit of INR deviation. Further still, this article discusses the evaluation techniques of taking into account the prothrombin ratio (PR) and the mean normal prothrombin time (MNPT), i.e., the geometric mean of normal plasma samples.
The discrepancies related to the use of the INR are further studied and described in the technical article of V. L. NG et al entitled, "Highly Sensitive Thromboplastins Do Not Improve INR Precision," published in American Journal of Clinical Pathology, 1998; 109, No. 3, 338-346 and herein incorporated by reference. In this article, the clinical significance of INR discordance is examined with the results being tabulated in Table 4 therein and which are analyzed to conclude that the level of discordance for paired values of individual specimens tested with different thromboplastins disadvantageously range from 17% to 29%.
It is desired that a method for monitoring oral anticoagulant therapy be provided that does not have the drawbacks of requiring the determination of the INR and ISI parameters and that does not suffer from the relatively high (13%) error sometimes occurring because of the use of these INR and ISI parameters with the exponents used in their determination.
Accordingly, it is a primary object of the present invention to provide a method and apparatus therefor, for accurate, yet simple, monitoring of oral anticoagulant therapy without any of the drawbacks and disadvantages of the prior art monitoring that relied on the INR and ISI parameters.
This invention relates to the inventions disclosed in U.S. Pat. Nos. 3,905,769 ('769) of Sep. 16, 1975; 5,197,017 ('017) dated Mar. 23, 1993; and 5,502,651 ('651) dated Mar. 26, 1996, all issued to Wallace E. Carroll and R. David Jackson, and all of which are incorporated herein by reference. Further, the invention relates to the previously mentioned cross-referenced applications. The present application discloses a method and an apparatus for monitoring anticoagulant therapy that uses some of the features of the apparatus shown and described in all of the earlier patents.